Much lower prevalence and mortality of chronic obstructive pulmonary disease in Japan than in the US despite higher smoking rates: A meta analysis/systematic review.

BACKGROUND: A recent systematic review showed Japan's mortality from chronic obstructive pulmonary disease (COPD) is the lowest among 204 countries, despite notably higher smoking rates in men in Japan than in the US. This study aims to compare (1) trends in smoking rates, (2) trends in COPD mortality, and (3) the spirometry-based COPD prevalence in the general adult population between Japan and the US. METHODS: Age- and sex-specific smoking rates from the 1980s through 2010s and COPD mortality from 1999 through 2019 were obtained from national surveys and official statistics (International Classification of Diseases-10th codes J40-44), respectively. A systematic review and meta-analysis was performed to estimate COPD prevalence in Japan, while the National Health and Nutrition Examination Survey 2007-2012 was used for the US. A fixed ratio of 0.7 of forced expiratory volume in the first second of forced vital capacity was used to define COPD. RESULTS: Over the past four decades, men in Japan consistently had 20-30% higher smoking rates than their US counterparts. From 1999-2019, age-adjusted COPD mortality in men in Japan was only a third of the US, whereas that in women was less than a tenth in 2019. Synthesizing data from 11 studies, involving 89,955 participants, Japan's COPD prevalence was more than 10% lower than in the US in almost all age groups for both sexes. CONCLUSIONS: This study showed markedly lower rates of COPD in Japan than in the US. Investigating factors contributing to the paradoxical observations could lead to advancing COPD risk reduction strategies.

A data-driven approach finds RNA polymerase III antibody and tendon friction rubs as enrichment tools for early diffuse scleroderma trials.

OBJECTIVE: Clinical trials in early diffuse SSc have consistently shown a placebo group response with a declining modified Rodnan skin score (mRSS), with negative outcomes. Our objective was to identify strategies using clinical characteristics or laboratory values to improve trial design. METHODS: We identified early diffuse SSc patients first seen at the University of Pittsburgh from 1980-2015. Eligible patients had ≥3 visits, with at least two mRSS scores within the first year of follow-up. We performed Kaplan-Meier analyses, group-based trajectory analysis of mRSS scores, followed by multivariable regression analysis and classification tree analysis. We applied the results to the abatacept in early diffuse systemic sclerosis (ASSET) trial outcome data. RESULTS: We identified 403 patients with <18 months, and 514 with <36 months disease duration. The median number of mRSS follow-up scores was 14 (interquartile range 8, 25). All methodologic approaches identified skin thickness progression rate, RNA polymerase III (RNAP3) antibody positivity and presence of tendon friction rubs (TFR) as predictors of mRSS trajectory over 5 years of follow-up, and thereby as potential enrichment variables. When applied to the ASSET data, adjustment for both RNAP3 and TFR demonstrated reduction of the placebo mRSS response, particularly at 6 months. A significant difference in the ACR Composite Response Index in Systemic Sclerosis (CRISS) score was found with adjustment by RNAP3 at 6 months, and TFR or RNAP3 at 12 months. CONCLUSION: Adjustment for both RNAP3 and TFR predicts mRSS trajectory and diminished the mRSS decline in ASSET placebo group, and identified significant differences in CRISS. RNAP3, particularly, is a stratification or enrichment approach to improve early diffuse SSc trial design.

Effects of inpatient rehabilitation after acute care on functional and quality-of-life outcomes in children with severe traumatic brain injury.

OBJECTIVE: Few studies have assessed the effectiveness of the rehabilitation process in children surviving severe traumatic brain injury (TBI). We evaluated whether receiving inpatient rehabilitation after acute hospitalization was associated with better functional outcomes compared to receiving only non-inpatient rehabilitation in children with severe TBI and explored an effect modification for Glasgow Coma Scale (GCS) score at hospital discharge. METHODS: We included 254 children who received rehabilitation following severe TBI from a multinational observational study. The Pediatric Glasgow Outcome Scale - Extended (GOS-E Peds), parent/guardian-reported and child-reported Pediatric Quality of Life Inventory (PedsQL) at 12 months post-injury were assessed and described using summary statistics. Unadjusted and propensity score-weighted linear/ordinal logistic regression modeling were also performed. RESULTS: 180 children received inpatient rehabilitation and 74 children received only non-inpatient rehabilitation after acute hospitalization. Among children with a GCS<13 at discharge, those receiving inpatient rehabilitation had a more favorable GOS-E Peds score (OR = 0.12, p = 0.045). However, no such association was observed in children with a higher GCS. We found no differences in PedsQL scores between rehabilitation groups. CONCLUSIONS: Future studies are warranted to confirm the benefits of inpatient rehabilitation for children with more severely impaired consciousness when medically stable.

Defining the optimal disease duration of early diffuse systemic sclerosis for clinical trial design.

OBJECTIVES: Clinical trials in early diffuse cutaneous systemic sclerosis (SSc) using the modified Rodnan skin score (mRSS) as the primary outcome measure have most often been negative. We wanted to assess how the definition of disease onset (first SSc manifestation vs first non-Raynaud manifestation) and varying lengths of disease duration at trial entry as an inclusion criteria functioned. Our objective was to optimize trial inclusion criteria. METHODS: We used the prospective, observational University of Pittsburgh Scleroderma Cohort to identify early diffuse SSc patients first evaluated between 1980 and 2015. All had <3 years from first SSc (n = 481) or first non-Raynaud manifestation (n = 514) and three or more mRSS scores. We used descriptive, survival and group-based trajectory analyses to compare the different definitions of disease onset and disease duration as inclusion criteria for clinical trials. RESULTS: There was no appreciable difference between using first SSc manifestation compared with first non-Raynaud manifestation as the definition of disease onset. Compared with other disease durations, <18 months of disease had >70% of patients fitting into trajectories with worsening cutaneous disease over 6 months of follow-up. Longer disease durations demonstrated the majority of patients with trajectories showing an improvement in mRSS (regression to the mean) over 6 months. CONCLUSIONS: Regardless of whether the first SSc or first non-Raynaud manifestation is used to define disease onset, duration of <18 months at enrolment is preferable. A longer disease duration criterion more frequently results in regression to the mean of the mRSS score, and likely contributes to negative trial outcomes.

Disparities in Health Care Utilization of Adults With Traumatic Brain Injuries Are Related to Insurance, Race, and Ethnicity: A Systematic Review.

OBJECTIVE: To characterize racial/ethnic and insurance disparities in the utilization of healthcare services among US adults with traumatic brain injury (TBI). METHODS: The PubMed database was used to search for articles that directly examined the association between race/ethnicity and insurance disparities and healthcare utilization among patients with TBI. Eleven articles that met the criteria and were published between June 2011 and June 2016 were finally included in the review. RESULTS: Lack of insurance was significantly associated with decreased use of inhospital and posthospital healthcare services among patients with TBI. However, mixed results were reported for the associations between insurance types and healthcare utilization. The majority of studies reported that racial/ethnic minorities were less likely to use inhospital and posthospital healthcare services, while some studies did not indicate any significant relation between race/ethnicity and healthcare utilization among patients with TBI. CONCLUSIONS: This review provides evidence of a relation between insurance status and healthcare utilization among US adults with TBI. Insurance status may also account for some portion of the relation between race/ethnicity and healthcare utilization.

Optimization Design Method of a New Stabilized Platform Based on Missile-borne Semi-Strap-down Inertial Navigation System.

At present, existing wide range Micro-Electro-Mechanical-Systems (MEMS) inertial sensors have relatively lower precision and direct measurement of the missile's high-rotation motion inevitably uses a large-range sensor. To achieve high-precision navigation, this paper proposes a novel Semi-strap-down Stabilized Platform (SSP) based on the Missile-borne Semi-Strap-down Inertial Navigation System, which is used to mount sensors and lowers sensor range requirements through isolating the high-rotational motion of missile. First, the author innovatively puts forward a dynamic model under missile-borne environment, then analyses the influence of SSP quality on the range of gyro according to the dynamic model of the SSP. Finally, when the angle of attack of the missile is 2°, the best quality of the SSP with minimum roll angular rate amplitude was calculated through the Runge-Kutta method and the mass gradient control method. Experiments have been carried out by using a high-precision, tri-axial flight simulation turntable to validate the viability of the method. Experiments show that under the same conditions, the angular velocity of the new optimized SSP with the best quality design is reduced to 1/3 of the unoptimized SSP, and the measured roll angle error is reduced to 60% of the unoptimized measurement. The results indicate that the novel SSP has better performance segregating the high-speed rotational motion, and provides theoretical guidance for the high-precision small-range sensor instead of the low-precision wide-range sensor. In addition, the first proposed SSP quality selection method creates a new idea for the improvement of the positioning accuracy in the missile-borne environment.

Effects of inpatient rehabilitation after acute care on motor, neuropsychological and behavioral outcomes in children with severe traumatic brain injury.

PURPOSE: An observational study of children with severe traumatic brain injury (TBI) (Approaches and Decisions in Acute Pediatric TBI [ADAPT] Trial) demonstrated the benefits of inpatient rehabilitation on functional outcomes for those with more severely impaired consciousness when medically stable. We conducted a secondary analysis to assess whether using an inpatient rehabilitation or skilled nursing facility after acute hospitalization was associated with better motor, neuropsychological, and behavioral outcomes compared to receiving only non-inpatient rehabilitation among children with severe TBI. MATERIALS AND METHODS: We included 180 children who used an inpatient rehabilitation or skilled nursing facility and 74 children who only received non-inpatient rehabilitation from the ADAPT trial. At 12 months post-injury, children underwent tests of motor skills, intellectual functioning, verbal learning, memory, processing speed, and cognitive flexibility. Parents/guardians rated children's executive function and behaviors. We performed inverse probability weighting to adjust for potential confounders. RESULTS: No significant differences were found in any motor, neuropsychological, or behavioral measures between children receiving inpatient rehabilitation and children receiving only non-inpatient rehabilitation. CONCLUSIONS: Analyses of comprehensive outcomes did not show differences between children receiving inpatient rehabilitation and children receiving only non-inpatient rehabilitation, suggesting a need for more research on specific components of the rehabilitation process.

Our study showed no differences in motor, neuropsychological, or behavioral outcomes at 12 months after severe traumatic brain injury (TBI) between children using an inpatient rehabilitation or skilled nursing facility and children receiving only non-inpatient rehabilitation after acute hospitalization.Children surviving severe TBI should be evaluated for the need of inpatient and outpatient rehabilitation therapies at discharge from an acute care hospital.Children with rehabilitation requirements after severe TBI should be followed up periodically to ensure the continuity of care and reduce the gaps to the needed rehabilitation therapies.

Validation of an Algorithm to Identify Venous Thromboembolism in Health Insurance Claims Data Among Patients with Rheumatoid Arthritis.

Purpose: Health insurance claims databases provide an opportunity to study uncommon events, such as venous thromboembolism (VTE), in large patient populations. This study evaluated case definitions for identifying VTE among patients treated for rheumatoid arthritis (RA) using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes in claims data. Patients and Methods: Study participants were insured adults who received treatment for and had a diagnosis of RA between 2016 and 2020. After a 6-month covariate assessment window, patients were observed for ≥1 month until health plan disenrollment, occurrence of a presumptive VTE, or end of the study (12/31/2020). Presumptive VTEs were identified using predefined algorithms based on ICD-10-CM diagnosis codes, anticoagulant use, and care setting. Medical charts were abstracted to confirm the VTE diagnosis. Performance of primary and secondary (less stringent) algorithms was assessed by calculating the positive predictive value (PPV; primary and secondary objectives). Additionally, a linked electronic health record (EHR) claims database and abstracted provider notes were used as a novel alternative source to validate claims-based outcome definitions (exploratory objective). Results: A total of 155 charts identified with the primary VTE algorithm were abstracted. The majority of patients were female (73.5%), with mean (standard deviation) age 66.4 (10.7) years and Medicare insurance (80.6%). Obesity (46.8%), ever smoking (55.8%), and prior evidence of VTE (28.4%) were commonly reported in medical charts. The PPV for the primary VTE algorithm was 75.5% (117/155; 95% confidence interval [CI], 68.7%, 82.3%). A less stringent secondary algorithm had a PPV of 52.6% (40/76; 95% CI, 41.4%, 63.9%). Using an alternative EHR-linked claims database, the primary VTE algorithm PPV was lower, potentially due to the unavailability of relevant records for validation. Conclusion: Administrative claims data can be used to identify VTE among patients with RA in observational studies.

CircRNAs in Lung Adenocarcinoma: Diagnosis and Therapy.

Lung adenocarcinoma (LUAD) is the common histological subtype of non-small-cell lung carcinoma (NSCLC). Circular RNAs (circRNAs) represent a new class of non-coding RNAs (ncRNAs) involved in the development of cancer. Accumulating evidence indicated that a large number of circular RNAs were found to be involved in many biological processes, including tumor initiation, proliferation and progression. These circRNAs present great potentials as new biomarkers and vital targets for disease diagnosis and prognosis. In this review, we mainly focus on the differentially expressed circRNAs and their functions in the pathogenesis of LUAD, which makes it possible for the utility of circRNAs as novel biomarkers for early diagnosis and therapy. Especially, it is helpful to develop circRNAs as crucial therapeutic targets, thus providing a promising biomedical application in the field of cancer gene therapy.

Unicompartmental knee arthroplasty is superior to high tibial osteotomy for the treatment of medial unicompartmental osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are widely used for the treatment of medial unicompartmental knee osteoarthritis (OA). However, the best approach remains controversial. This study aimed to present a systematic review and a meta-analysis to directly compare the clinical outcomes between HTO and UKA. We hypothesized that the clinical outcomes after UKA and HTO would be similar. METHODS: Electronic databases (Web of Science, PubMed, Embase, CENTRAL, and Biosis Preview) were searched for related studies published before November 30, 2021. Retrospective and prospective studies that directly compared the postoperative outcomes between UKA and HTO were included. Odds ratio (ORs) and 95% confidence interval (CIs) for complications, revision to total knee arthroplasty (TKA), and weighted mean difference (MD) and 95% CIs in range of motion (ROM), pain, walking speed and function score were evaluated. Two reviewers independently assessed the quality of the studies. Subgroup and sensitivity analyses were performed to explore the heterogeneity. RESULTS: Twenty-three retrospective and 6 prospective studies were included. A total of 3004 patients (3084 knees) were evaluated for comparison. Complications (OR, 4.88, 95% CI: 2.92-6.86) were significantly greater in the HTO group than in the UKA group. Postoperative function scores including Lysholm score (MD, -2.78, 95% CI: -5.37 to -0.18) and Hospital for Special Surgery (HSS) score (MD, -2.80, 95% CI: -5.39 to -0.20) were significantly lower in the HTO group than the UKA group. The postoperative ROM was similar between HTO and mobile-bearing UKA (MD, -3.78, 95% CI: -15.78 to 8.22). However, no significant differences were observed between the HTO and UKA group in terms of postoperative pain, walking speed, and revision to TKA. CONCLUSIONS: UKA is superior to HTO in minimizing complications and enhancing postoperative function scores. Mobile-bearing UKA has a similar ROM compared with HTO. Both HTO and UKA provide satisfactory clinical outcomes in terms of walking speed, relieving pain, and revision to TKA. UKA appears to be more suitable for the elderly, and both mobile-bearing UKA and HTO are viable surgical options for younger active individuals.

Lonafarnib Inhibits Farnesyltransferase via Suppressing ERK Signaling Pathway to Prevent Osteoclastogenesis in Titanium Particle-Induced Osteolysis.

Wear debris after total joint arthroplasty can attract the recruitment of macrophages, which release pro-inflammatory substances, triggering the activation of osteoclasts, thereby leading to periprosthetic osteolysis (PPOL) and aseptic loosening. However, the development of pharmacological strategies targeting osteoclasts to prevent periprosthetic osteolysis has not been fruitful. In this study, we worked toward researching the effects and mechanisms of a farnesyltransferase (FTase) inhibitor Lonafarnib (Lon) on receptor activator of nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis and bone resorption, as well as the impacts of Lon on titanium particle-induced osteolysis. To investigate the impacts of Lon on bone resorption and osteoclastogenesis in vitro, bone marrow macrophages were incubated and stimulated with RANKL and macrophage colony-stimulating factor (M-CSF). The influence of Lon on osteolysis prevention in vivo was examined utilizing a titanium particle-induced mouse calvarial osteolysis model. The osteoclast-relevant genes expression was explored by real-time quantitative PCR. Immunofluorescence was used to detect intracellular localization of nuclear factor of activated T cells 1 (NFATc1). SiRNA silence assay was applied to examine the influence of FTase on osteoclasts activation. Related signaling pathways, including NFATc1 signaling, NF-κB, mitogen-activated protein kinases pathways were identified by western blot assay. Lon was illustrated to suppress bone resorptive function and osteoclastogenesis in vitro, and it also reduced the production of pro-inflammatory substances and prevented titanium particle-induced osteolysis in vivo. Lon decreased the expression of osteoclast-relevant genes and suppressed NFATc1 nuclear translocation and auto-amplification. Mechanistically, Lon dampened FTase, and inhibition of FTase reduced osteoclast formation by suppressing ERK signaling. Lon is a promising treatment option for osteoclast-related osteolysis diseases including periprosthetic osteolysis by targeted inhibition of FTase through suppressing ERK signaling.

Comparison of Intracranial Pressure Measurements Before and After Hypertonic Saline or Mannitol Treatment in Children With Severe Traumatic Brain Injury.

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol. Objectives: To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP). Design, Setting, and Participants: In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021. Interventions: Boluses of HTS and mannitol were administered. Main Outcomes and Measures: Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments. Results: A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted ß, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted ß, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted ß, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted ß, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted ß, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis. Conclusions and Relevance: In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.

Characteristics Associated with the Use of an Inpatient Rehabilitation or Skilled Nursing Facility after Acute Care in Children with Severe Traumatic Brain Injury.

To characterize inpatient rehabilitation services for children with severe traumatic brain injury (TBI), we included 254 children, whose parents/guardians reported receipt of rehabilitation within a 12-month follow-up period, from a multinational observational study. Children discharged to an inpatient rehabilitation or skilled nursing facility after acute care were classified into the "inpatient rehabilitation" group, and children discharged home after acute care were classified into the "non-inpatient rehabilitation" group. Multivariable regression analyses determined the associations of sociodemographic and clinical characteristics with rehabilitation groups. Children receiving inpatient rehabilitation had a shorter length of acute hospitalization. Children from the UK were less likely to receive inpatient rehabilitation compared to children from the US. Future studies are warranted to extend current findings by identifying the reasons behind differential access to inpatient rehabilitation among children with severe TBI.

In-Hospital Mobility Variations Across Primary Diagnoses Among Older Adults.

OBJECTIVES: To examine the relationship between primary diagnoses and mobility impairment and recovery among hospitalized older adults. DESIGN: Prospective cohort study. SETTING: UF Health Shands Hospital, an 852-bed level I trauma center located in Gainesville, Florida. PARTICIPANTS: A total of 18,551 older adults (≥65 years) with 29,148 hospitalizations between January 2009 and April 2014. MEASUREMENTS: Incident and discharge mobility impairment and recovery were assessed using the Braden activity subscale score that was recorded by the nursing staff at every shift change: approximately 3 times per day. Primary diagnosis ICD-9 codes were used as predictors and recategorized by using the Agency for Health Care Research and Quality Clinical Classification Software. RESULTS: Of the 15,498 hospital records in which the patient was initially observed to "walk frequently," 3186 (20.6%) developed incident mobility impairment (chair-fast or bedfast). Primary diagnoses with a surgical or invasive procedure were the most prevalent (77.2%) among the hospital observations with incident mobility impairment; otherwise, primary diagnoses without surgery were much more associated with discharge mobility impairment (59%). The highest incidence of mobility impairment occurred in patients with heart valve disorders and aortic and peripheral/visceral artery aneurysms (6.24 and 6.05 events per 30 person-days, respectively); septicemia showed the highest incidence rate for mobility limitation at discharge (0.94 events per 30 person-days). Mobility impairment was observed in 13,650 (46.8% of total) records at admission and 5930 (43.44%) were observed to recover to a state of walking occasionally or frequently. Osteoarthritis and cancer of gastrointestinal organs/peritoneum had the highest incidence rate for mobility recovery (7.68 and 5.63 events per 30 person-days respectively). CONCLUSIONS: Approximately 1 of 5 patients who were mobile at admission became significantly impaired during hospitalization. However, approximately half (43.4%) of patients observed to have mobility impairment at admission recovered during hospitalization. Conditions most associated with mobility impairment and recovery are varied, but older patients hospitalized for septicemia and cardiovascular diseases with surgery (heart valve disorders and aortic/peripheral/visceral artery aneurysms) appear to be at most risk for incident mobility impairment that did not recover at discharge.